Nutritional support for wound healing.

Altern Med Rev. 2003 Nov;8(4):359-77.

MacKay D, Miller AL.

Thorne Research, Inc., PO Box 25, Dover, ID 83825, USA. duffy@thorne.com

Healing of wounds, whether from accidental injury or surgical intervention, involves the activity of an intricate network of blood cells, tissue types, cytokines, and growth factors. This results in increased cellular activity, which causes an intensified metabolic demand for nutrients. Nutritional deficiencies can impede wound healing, and several nutritional factors required for wound repair may improve healing time and wound outcome. Vitamin A is required for epithelial and bone formation, cellular differentiation, and immune function. Vitamin C is necessary for collagen formation, proper immune function, and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain reduces edema, bruising, pain, and healing time following trauma and surgical procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic acid production in the wound. Adequate dietary protein is absolutely essential for proper wound healing, and tissue levels of the amino acids arginine and glutamine may influence wound repair and immune function. The botanical medicines Centella asiatica and Aloe vera have been used for decades, both topically and internally, to enhance wound repair, and scientific studies are now beginning to validate efficacy and explore mechanisms of action for these botanicals. To promote wound healing in the shortest time possible, with minimal pain, discomfort, and scarring to the patient, it is important to explore nutritional and botanical influences on wound outcome.

PMID: 14653765 [PubMed - in process]

Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults.

Phytomedicine. 2002 Dec;9(8):681-6.

Walker AF, Bundy R, Hicks SM, Middleton RW.

Hugh Sinclair Unit of Human Nutrition, The University of Reading, UK. a.f.walker@reading.ac.uk

There is preliminary clinical evidence to support the contention that the anti-inflammatory and analgesic properties of bromelain help to reduce symptoms of osteo- and rheumatoid arthritis. However, there have been no controlled studies of its effects on joint health in healthy subjects who lack such diagnosis. The current study investigated the effects of bromelain on mild acute knee pain of less than 3 months duration in otherwise healthy adults. The study was an open, dose-ranging postal study in volunteers who had been recruited through newspaper and magazine articles. Two validated questionnaires (WOMAC knee health Index and the Psychological Well-Being Index) were completed at baseline and after one month's intervention with bromelain, randomly allocated to volunteers as either 200 mg or 400 mg per day. Seventy seven subjects completed the study. In both treatment groups, all WOMAC symptom dimension scores were significantly reduced compared with baseline, with reductions in the final battery (total symptom score) of 41 and 59% (P = 0.0001 and <0.0001) in the low and high dose groups respectively. In addition, improvements in total symptom score (P = 0.036) and the stiffness (P = 0.026) and physical function (P = 0.021) dimensions were significantly greater in the high-dose (400 mg per day) compared with the low-dose group. Compared to baseline, overall psychological well-being was significantly improved in both groups after treatment (P = 0.015 and P = 0.0003 in the low and high dose groups respectively), and again, a significant dose-response relationship was observed. We conclude that bromelain may be effective in ameliorating physical symptoms and improving general well-being in otherwise healthy adults suffering from mild knee pain in a dose-dependant manner. Double blind, placebo-controlled studies are now warranted to confirm these results.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 12587686 [PubMed - indexed for MEDLINE]

Nutritional and botanical modulation of the inflammatory cascade--eicosanoids, cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy.

Integr Cancer Ther. 2002 Mar;1(1):7-37; discussion 37.

Wallace JM.

Nutritional Solutions, Inc., 2935 North, 1000 East, North Logan, UT 84341, USA. BTnutrition@aol.com

Emerging on the horizon in cancer therapy is an expansion of the scope of treatment beyond cytotoxic approaches to include molecular management of cancer physiopathology. The goal in these integrative approaches, which extends beyond eradicating the affected cells, is to control the cancer phenotype. One key new approach appears to be modulation of the inflammatory cascade, as research is expanding that links cancer initiation, promotion, progression, angiogenesis, and metastasis to inflammatory events. This article presents a literature review of the emerging relationship between neoplasia and inflammatory eicosanoids (PGE2 and related prostaglandins), with a focus on how inhibition of their synthesizing oxidases, particularly cyclooxygenase (COX), offers anticancer actions in vitro and in vivo. Although a majority of this research emphasizes the pharmaceutical applications of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors, these agents fail to address alternate pathways available for the synthesis of proinflammatory eicosanoids. Evidence is presented that suggests the inhibition of lipoxygenase and its by-products-LTB4, 5-HETE, and 12-HETE-represents an overlooked but crucial component in complementary cancer therapies. Based on the hypothesis that natural agents capable of modulating both lipoxygenase and COX may advance the efficacy of cancer therapy, an overview and discussion is presented of dietary modifications and selected nutritional and botanical agents (notably, omega-3 fatty acids, antioxidants, boswellia, bromelain, curcumin, and quercetin) that favorably influence eicosanoid production.

PMID: 14664746 [PubMed - in process]

Respiratory and allergic diseases: from upper respiratory tract infections to asthma.

Prim Care. 2002 Jun;29(2):231-61.

Jaber R.

Division of Wellness and Chronic Illness, Department of Family Medicine, University Hospital and Medical Center, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8461, USA. rjaber@notes.cc.sunysb.edu

Patients with asthma and allergic rhinitis may benefit from hydration and a diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3 fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds), onions, and fruits and vegetables (at least five servings a day). Physicians may need to be more cautious when prescribing antibiotics to children in their first year of life when they are born to families with a history of atopy. More research is needed to establish whether supplementation with probiotics (lactobacillus and bifidobacterium) during the first year of life or after antibiotic use decreases the risk of developing asthma and allergic rhinitis. Despite a theoretic basis for the use of vitamin C supplements in asthmatic patients, the evidence is still equivocal, and long-term studies are needed. The evidence is stronger for exercise-induced asthma, in which the use of vitamin C supplementation at a dosage of 1 to 2 g per day may be helpful. It is also possible that fish oil supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day, also may be helpful to some patients with asthma. Long-term studies of fish oil and vitamin C are needed for more definite answers. For the patient interested in incorporating nutritional approaches, vitamin C and fish oils have a safe profile. However, aspirin-sensitive individuals should avoid fish oils, and red blood cell magnesium levels may help in making the decision whether to use additional magnesium supplements. Combination herbal formulas should be used in the treatment of asthma with medical supervision and in collaboration with an experienced herbalist or practitioner of TCM. Safe herbs, such as Boswellia and gingko, may be used singly as adjuncts to a comprehensive plan of care if the patient and practitioner have an interest in trying them while staying alert for drug-herb interactions. No data on the long-term use of these single herbs in asthma exist. For the motivated patient, mind-body interventions such as yoga, hypnosis, and biofeedback-assisted relaxation and breathing exercises are beneficial for stress reduction in general and may be helpful in further controlling asthma. Encouraging parents to learn how to massage their asthmatic children may appeal to some parents and provide benefits for parents and children alike. Acupuncture and chiropractic treatment cannot be recommended at this time, although some patients may derive benefit because of the placebo effect. For patients with allergic rhinitis, there are no good clinical research data on the use of quercetin and vitamin C. Similarly, freeze-dried stinging nettle leaves may be tried, but the applicable research evidence also is poor. Further studies are needed to assess the efficacy of these supplements and herbs. Homeopathic remedies based on extreme dilutions of the allergen may be beneficial in allergic rhinitis but require collaboration with an experienced homeopath. There are no research data on constitutional homeopathic approaches to asthma and allergic rhinitis. Patients with COPD are helped by exercise, pulmonary rehabilitation, and increased caloric protein and fat intake. Vitamin C and n-3 supplements are safe and reasonable; however, studies are needed to establish their efficacy in COPD. On the other hand, there are convincing data in favor of N-acetyl-cysteine supplementation for the patient with COPD at doses ranging between 400 and 1200 mg daily. Red blood cell magnesium levels may guide the use of magnesium replacement. The use of L-carnitine and coenzyme Q10 in patients with COPD needs further study. The addition of essential oils to the dietary regimen of patients with chronic bronchitis is worth exploring. Patients with upper respiratory tract infections can expect a shorter duration of symptoms by taking high doses of vitamin C (2 g) with zinc supplements, preferably the nasal zinc gel, at the onset of their symptoms. Adding an herb such as echinacea or Andrographis shortens the duration of the common cold. The one study on Elderberry's use for the flu was encouraging, and the data on the homeopathic remedy Oscillococcinum interesting, but more studies should be performed. Saline washes may be helpful to patients with allergic rhinitis and chronic sinusitis. Patients also may try the German combination (available in the United States) of elderberry, vervain, gentian, primrose, and sorrel that has been tested in randomized clinical trials. Bromelain is safe to try; the trials of bromelain supplementation were promising but were never repeated. The preceding suggestions need to be grounded in a program based on optimal medical management. Patients need to be well educated in the proper medical management of their disease and skilled at monitoring disease stability and progress. Asthmatic patients need to monitor their bronchodilator usage and peak flow meter measurements to step up their medical treatment in a timely manner, if needed. Patients welcome physician guidance when exploring the breadth of treatments available today. A true patient-physician partnership is always empowering to patients who are serious about regaining their function and health.

Publication Types:

• Review
• Review, Tutorial

PMID: 12391710 [PubMed - indexed for MEDLINE]

Administration of proteolytic enzymes bromelain and trypsin diminish the number of CD4+ cells and the interferon-gamma response in Peyer's patches and spleen in endotoxemic balb/c mice.

Cell Immunol. 2002 Feb;215(2):113-9.

Manhart N, Akomeah R, Bergmeister H, Spittler A, Ploner M, Roth E.

Department of Surgical Research, University Vienna, Austria. nicole.manhart@akh-wien.ac.at

Recent publications revealed that bromelain exerts a marked effect on T-cell response by inhibiting T-cell signal transduction. These experimental studies may help to explain former clinical investigations showing that Phlogenzym (PHL), a preparation consisting of the proteases bromelain and trypsin and the antioxidant rutosid, ameliorate certain diseases with an underlying inflammatory process. In this study, we showed that orally administered PHL significantly reduced lymphocyte subpopulations in Peyer's patches (PPs) of healthy and endotoxemic mice. Similarly, the number of splenic lymphocytes in endotoxin-boostered mice was significantly lowered by PHL. The effect of PHL was more pronounced on T cells than on B cells leading especially to a diminution of CD4+ cells. Moreover, PHL pretreatment decreased IFN-gamma mRNA in PPs and spleen of endotoxemic mice. These results reveal that PHL may ameliorate inflammatory process by reducing the number of CD4+ cells and by diminishing INF-gamma mRNA levels.

PMID: 12202148 [PubMed - indexed for MEDLINE]

Effects of sources of protein and enzyme supplementation on protein digestibility and chyme characteristics in broilers.

Br Poult Sci. 2002 Jul;43(3):424-31.

Yu B, Lee TT, Chiou PW.

Department of Animal Science, National Chung-Hsing University, 250 Kuo-Kuang Road, Taichung 402, Taiwan.

1. The purpose of this study was to evaluate the effects of protein source and enzyme supplementation on protein digestibility and chyme characteristics in broilers. 2. One hundred and twenty growing (13 d old) and 60 finishing (34 d old) Arbor Acre strain commercial male broilers were selected and placed into individual metabolic cages. 3. The experiment was a 5 x 2 factorial arrangement with 5 different sources of protein: casein, fish meal, soybean meal (SBM), soy protein concentrate (SPC), maize gluten meal (MGM) and two levels of protease (bromelain), 0 and 65 CDU/kg diets. 4. The diets were iso-nitrogenous and semi-purified, with Cr2O3 as an indicator for determination of ileal digestibility and chyme characteristics. 5. Apparent ileal protein digestibility (AIPD) in both growing and finishing chickens was highest on the casein diet, followed by fish meal, SBM, SPC and MGM. 6. Enzyme inclusion did not improve protein digestibility, but significantly decreased the digesta pH value in the gizzard and increased pH in the ileum in the 3-week-old broilers. 7. The digesta pH values in the gizzard and duodenum were significantly lower in the SBM and fish meal groups compared with the other protein groups. The molecular weight distribution pattern of the soluble protein in the chyme of the gastrointestinal (GI) segments showed a similar trend, regardless of the enzyme inclusion or the stage of growth. 8. The molecular weight profile of soluble protein changed dynamically in the casein fed broilers from the gizzard to ileum and the low molecular weight proteins, < 7 kDa, reached maximum levels at the ileum. The molecular weight profile of the soluble protein in the SBM and SPC changed between the jejunum and the ileum and in the intermediate molecular soluble protein weight (7 to 10 kDa) was significantly decreased. This indicated that the hydrolysis process began from the middle to the posterior end of the small intestine. 9. Similar profiles were also shown with fish meal protein. The pattern of distribution, however, did not show any prominent change in the GI segments of the MGM group. 10. The pepsin, trypsin and chymotrypsin protease activity in the gizzard and duodenum were highest in the casein group and lowest in the MGM group as compared with the other protein groups. 11. The rate change in the patterns of molecular weight distribution in soluble protein and the digestive enzyme activity provide indications of the partial digestibility of different protein sources. The exogenous enzyme, bromelain, did not show any beneficial effect on protein digestion.

PMID: 12195802 [PubMed - indexed for MEDLINE]

Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthrosis of knee joint: an open randomized controlled clinical trial.

J Assoc Physicians India. 2001 Jun;49:617-21.

Tilwe GH, Beria S, Turakhia NH, Daftary GV, Schiess W.

Department of Medicine, GS Medical College and KEM Hospital, Mumbai.

OBJECTIVE: To compare the efficacy and tolerability of an oral enzyme preparation (Phlogenzym) with that of an NSAID (diclofenac) in the treatment of active osteoarthrosis. METHODS: Prospective, randomized, controlled, single-blind study of seven weeks duration at a tertiary care centre wherein 50 patients aged 40-75 years, with activated osteoarthrosis of knee joint were randomized to receive phlogenzym tablets (2-3 tablets, bid) or diclofenac sodium 50 mg bid for three weeks. RESULTS: At the end of therapy (three weeks) and at follow-up visit at seven weeks there was reduction in pain and joint tenderness and swelling in both groups, and slight improvement in the range of movement in the study group. The reduction in joint tenderness was greater (p < 0.05) in the study group receiving phlogenzym. CONCLUSION: Phlogenzym is as efficacious and well tolerated as diclofenac sodium in the management of active osteoarthrosis over three weeks of treatment.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 11584936 [PubMed - indexed for MEDLINE]

Preliminary comparison of bromelain and Ibuprofen for delayed onset muscle soreness management.

Clin J Sport Med. 2002 Nov;12(6):373-8.

Stone MB, Merrick MA, Ingersoll CD, Edwards JE.

Indiana State University, Terre Haute 47809, USA. athstone@isugw.indstate.edu

OBJECTIVE: The purpose of this study was to determine whether a common bromelain regimen or common ibuprofen regimen are effective in resolving pain and muscle dysfunction associated with delayed onset muscle soreness of the elbow flexors. DESIGN: A randomized, double-blinded, repeated measures design was used for this study. SETTING: The study was performed in the Sports Injury Research Lab at an NCAA Division I university. PARTICIPANTS: Forty subjects who had not participated in an upper body resistance-training program 3 months prior to the study, suffered pain or injury in the nondominant arm, or experienced an adverse response to nonsteroidal anti-inflammatory drugs or pineapple (bromelain source) were recruited. Thirty-nine subjects finished the study. INTERVENTIONS: Active range of motion (ROM), perceived pain, and peak concentric torque measurements of the nondominant arm were taken prior to and 24, 48, 72, and 96 hours following an eccentric exercise protocol of the elbow flexors. Subjects were assigned to one of four treatment groups (bromelain 300 mg t.i.d., ibuprofen 400 mg t.i.d., placebo t.i.d., and control) and began treatment immediately following the exercise protocol. MAIN OUTCOME MEASURES: No differences among treatments were observed for any of the dependent variables at any time. ROM deficits and pain peaked between 48 and 72 hours. Peak torque deficiencies were observed between 24 and 72 hours. CONCLUSIONS: Ingestion of bromelain and ibuprofen had no effect on elbow flexor pain, loss of ROM, or loss of concentric peak torque as a result of an eccentric exercise regimen.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 12466693 [PubMed - indexed for MEDLINE]

Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation.

Clin Immunol. 2002 Aug;104(2):183-90.

Hale LP, Greer PK, Sempowski GD.

Department of Pathology, Duke University, Durham, NC 27710, USA.

Bromelain is a natural proteinase preparation derived from pineapple stem that is marketed for oral use as a digestive aid and as an antiinflammatory agent. Bromelain treatment in vitro has been previously shown to selectively remove certain cell surface molecules that may affect lymphocyte migration and activation. This study reports the effects of bromelain on a broad range of cell surface molecules and on lymphocytes, monocytes, and granulocytes under physiologically relevant conditions. In vitro bromelain treatment of leukocytes in whole blood proteolytically altered 14 of 59 leukocyte markers studied. Constitutively expressed bromelain-sensitive molecules included CD7, CD8alpha, CD14, CD16, CD21, CD41, CD42a, CD44, CD45RA, CD48, CD57, CD62L, CD128a, and CD128b. The proteolytic effect of bromelain increased as the concentration of plasma decreased, with EC50 ranging from >1000 microg/ml for 100% plasma to approximately 1 microg/ml in the absence of plasma, indicating the presence of an inhibitor of bromelain in plasma. alpha2-macroglobulin purified from plasma mimicked the inhibitory effect of whole plasma on bromelain activity. If proteolysis is required for the antiinflammatory actions of oral bromelain, these data suggest that the required concentrations are more likely to be achieved locally in the gastrointestinal tract or in other tissue sites where the plasma concentration is low, rather than in the bloodstream. The cell surface molecules altered by bromelain are involved in leukocyte homing and cellular adhesion and activation. Thus bromelain could potentially exert an antiinflammatory effect by multiple mechanisms, including alterations in leukocyte migration and activation.

PMID: 12165279 [PubMed - indexed for MEDLINE]

In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in the inflammatory exudate in rats.

Pharmacology. 2002 May;65(2):83-6.

Gaspani L, Limiroli E, Ferrario P, Bianchi M.

Department of Pharmacology, University of Milan, Italy.

The effects of bromelain were examined in rats with subcutaneous carrageenin-induced inflammation. After oral in vivo administration, bromelain (10 and 20 mg/kg p.o.) induced a significant decrease of both PGE(2) and substance P concentrations in the exudate. When added to the inflammatory exudate in vitro, the drug (25, 50, 100 microg/ml) did not affect PGE(2) concentrations and induced an increase in the substance P levels. Our data indicate that bromelain reduces the production of two key mediators of inflammation. This effect does not seem to be related to a direct action of the drug on PGE(2) and SP released in the exudate in response to the inflammatory stimulus. Copyright 2002 S. Karger AG, Basel

PMID: 11937778 [PubMed - indexed for MEDLINE]

Bromelain: biochemistry, pharmacology and medical use.

Maurer HR.

Cell Mol Life Sci. 2001 Aug;58(9):1234-45.

Department of Biochemistry, Molecular Biology and Biotechnology, Institute of Pharmacy, Freie Universitat Berlin, Germany. hrmaurer@zedat.fu-berlin.de

Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases, demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. The active factors involved are biochemically characterized only in part. Due to its efficacy after oral administration, its safety and lack of undesired side effects, bromelain has earned growing acceptance and compliance among patients as a phytotherapeutical drug. A wide range of therapeutic benefits has been claimed for bromelain, such as reversible inhibition of platelet aggregation, angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis, pyelonephritis and enhanced absorption of drugs, particularly of antibiotics. Biochemical experiments indicate that these pharmacological properties depend on the proteolytic activity only partly, suggesting the presence of nonprotein factors in bromelain. Recent results from preclinical and pharmacological studies recommend bromelain as an orally given drug for complementary tumor therapy: bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity of monocytes against tumor cells from patients and by inducing the production of distinct cytokines such as tumor necrosis factor-a, interleukin (Il)-1beta, Il-6, and Il-8. In a recent clinical study with mammary tumor patients, these findings could be partially confirmed. Especially promising are reports on animal experiments claiming an antimetastatic efficacy and inhibition of metastasis-associated platelet aggregation as well as inhibition of growth and invasiveness of tumor cells. Apparently, the antiinvasive activity does not depend on the proteolytic activity. This is also true for bromelain effects on the modulation of immune functions, its potential to eliminate burn debris and to accelerate wound healing. Whether bromelain will gain wide acceptance as a drug that inhibits platelet aggregation, is antimetastatic and facilitates skin debridement, among other indications, will be determined by further clinical trials. The claim that bromelain cannot be effective after oral administration is definitely refuted at this time.

Publication Types:

• Review
• Review, Academic

PMID: 11577981 [PubMed - indexed for MEDLINE]

Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in human blood.

Cancer Chemother Pharmacol. 2001 Jul;47 Suppl:S10-5.

Desser L, Holomanova D, Zavadova E, Pavelka K, Mohr T, Herbacek I.

Institute of Cancer Research, University of Vienna, Austria. ldesser@hotmail.com

Therapy with oral proteolytic enzymes (OET) with combination drug products containing papain, bromelain, trypsin, and chymotrypsin has been shown to be beneficial in clinical settings such as radiotherapy-induced fibrosis, bleomycin pneumotoxicity and immunosuppression in cancer, all of which are nowadays known to be accompanied by excessive transforming growth factor-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) from the "slow" form into the "fast" form, whereby the "fast" form binds and inactivates TGF-beta irreversibly. In this study we have investigated the effect of OET on the concentration of TGF-beta1 in serum of patients with rheumatoid arthritis (RA) (n = 38), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta1 levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and latent TGF-beta1 in serum (r=0.8021; P<0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or patients with a normal level of TGF-beta1. In patients with elevated TGF-beta1 concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P < 0.005), in OMF (P < 0.05) and in HZ (P < 0.05). Conclusion: These results support the concept that OET is beneficial in diseases characterized in part by TGF-beta1 overproduction.

PMID: 11561866 [PubMed - indexed for MEDLINE]

Therapy with proteolytic enzymes in rheumatic disorders.

Leipner J, Iten F, Saller R.

BioDrugs. 2001;15(12):779-89.

Department of Natural Medicine, University Hospital, Zurich, Switzerland.

Plant extracts with a high content of proteolytic enzymes have been used in traditional medicine for a long time. Besides herbal proteinases, 'modern' enzyme therapy includes pancreatic enzymes. The therapeutic use of proteolytic enzymes is empirically based, but is also supported by scientific studies. This review provides an overview of preclinical and clinical trials of systemic enzyme therapy in rheumatic disorders. Studies of the use of proteolytic enzymes in rheumatic disorders have mostly been carried out on enzyme preparations consisting of combinations of bromelain, papain, trypsin and chymotrypsin. The precise mechanism of action of systemic enzyme therapy remains unresolved. The ratio of proteinases to antiproteinases, which is affected by rheumatic diseases, appears to be influenced by the oral administration of proteolytic enzymes, probably via induction of the synthesis of antiproteinases or a signal transduction of the proteinase-antiproteinase complex via specific receptors. Furthermore, there are numerous alterations of cytokine composition during therapy with orally administered enzymes resulting from immunomodulatory effects, which might be an indication of the efficacy of enzyme therapy. The results of various studies (placebo-controlled and comparisons with nonsteroidal anti-inflammatory drugs) in patients with rheumatic diseases suggest that oral therapy with proteolytic enzymes produces certain analgesic and anti-inflammatory effects. However, the results are often inconsistent. Nevertheless, in the light of preclinical and experimental data as well as therapeutic experience, the application of enzyme therapy seems plausible in carefully chosen patients with rheumatic disorders.

Publication Types:

• Review
• Review, Tutorial

PMID: 11784210 [PubMed - indexed for MEDLINE]

[Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling]

Acta Chir Orthop Traumatol Cech. 2001;68(1):45-9.

Kamenicek V, Holan P, Franek P.

Chirurgicke oddeleni nemocnice, Bilovec.

PURPOSE OF THE STUDY: The authors concentrate on the use of enzyme therapy in traumatology. They monitored SET efficiency in the treatment and prophylazis of swelling in the postoperative period after the internal fixation of fractures of long bones and compared it with the effect of standard antiswelling seu antioedematous drugs on the basis of aescin. MATERIAL: A group of 60 patients was followed after the fixation of long bones. The average age was 42 years (range, 12-79 years). Fractures were treated by intrameduilary fixation or by external fixators. The patients were split into two groups. In 30 patients only Phlogenzym was administered for the treatment and prevention of posttraumatic and postoperative swelling. Another 30 patients--the control group--were treated by standard antioedematic drugs on the basis of aescin. The same analgesics were applied in both groups. METHODS: The group of patients with systemic enzyme therapy were treated by Phlogenzym in the dosage 3 times 3 tablets in the first three days after operation and subsequently 3 times 2 tablets in the remaining follow-up period. In the postoperative period the changes of operated limb volume was monitored. The circumference of a limb was measured in the area of the largest oedema and 10 cm distally. Then the volume of this part of limb was calculated as the volume of conical frustum. The measurements were performed on postoperative days 1, 3, 5, 7, 10 and 14. The volume value of the 1st day was used as starting value (100%). The values of subsequent measurements were then compared to this starting value in both group of patients. Evaluation of the resorption of traumatic and postoperative haematoma and analgesis effect of Phlogenzym was also made. RESULTS: In the group of patients who were administered with Phlogenzym after operation the reduction of the posttraumatic and postoperative swelling was continuous and significantly faster in compared with patients of the control group. A remarkable difference was revealed by the measurement on 5th postoperative day--in patients treated by Phlogenzym the starting value of the volume of the operated in limb was reduced on average by almost 8%. In contrast, in the control group treated by standard drugs this value slightly increased above 100%. At the end of the first postoperative week the monitored volume was on average reduced by 12% in the SET group compared with 1.45% in the control group. At the end of the follow-up--on 14th postoperative day the volume was reduced in the SET group by almost 17% compared with 9% in the control group. There was also an evidently good analgesic effect of the drug. The total consumption of analgesics of patients in the SET group was significantly lower, particularly in the early postoperative period. In the course of the follow-up of both groups no marked differences were recorded in the changes of the volume of operated limbs in dependence on the method of fixation applied (intramedullary or external), sex of the patient or on the affected limb (lower or upper). The patients tolerated Phlogenzym very well, only one female patient suffered temporarily from poor digestion which, however, did not require to interrupt the administration of the drug. No other undesirable effects occurred. DISCUSSION: Fixation of long bones belongs to the most frequent operations in traumatological and orthopaedic departments of all levels. One of the factors which may have an unfavourable effect on the final result of fixation is a prolonged post-trauma or postoperative swelling. The results of the study prove a clearly positive effect of system enzymotherapy on the reduction of oedema accompanying the trauma and inflammation. The study proved a statistical significance of the acceleration of the reduction of oedema in patients treated by Phlogenzym as compared to the control group treated by a standard antioedematous drugs. CONCLUSION: The authors verified that systemic enzyme therapy could influence significantly the results of traumatological surgery. Simple administration per os, efficient oedema reduction and thus accelerated healing, antiophlogistic and analgesic effect--all these advantages justify the application of this therapeutic method what can be recommended as a part of the complex treatment in traumatology with both conservative and surgical approaches.

Publication Types:

• Clinical Trial
• Controlled Clinical Trial

PMID: 11706714 [PubMed - indexed for MEDLINE]

Bromelain is an accelerator of phagocytosis, respiratory burst and Killing of Candida albicans by human granulocytes and monocytes.

Eur J Med Res. 2001 May 29;6(5):193-200.

Brakebusch M, Wintergerst U, Petropoulou T, Notheis G, Husfeld L, Belohradsky BH, Adam D.

Dr. von Haunersches Kinderspital, Abtl. fur antimikrobielle Therapie und Infektionsimmunologie, Munich, Germany. Myga.Brakebusch@lrz.tum.de

OBJECTIVE: The aim of this study was to examine the influence of immuno modulating agents like bromelain and trypsin (e.g. Wobenzym on granulocyte and monocyte functions in healthy volunteers and patients with disorders of the humoral immuno system X-linked agammaglobulinaemia (XLA) and common variable immuno deficiency (CVID) and to find out whether the unspecific immunity could be improved by these enzymes. METHODS: In a whole-blood assay kinetics of phagocytosis, respiratory burst and killing (PBK) were measured in blood samples incubated with and without bromelain and trypsin (B/T) using Candida albicans as target organism. The time-reaction curves were analysed determining their gradient (T1) and their onset (T2) as well as the half effect time (HET). RESULTS: Phagocytes from patients with XLA showed a significantly accelerated basal phagocytosis (reduction of HET by 24% p < 0.001) compared to healthy controls. After incubation with B/T (10 microg/ml each) speed of phagocytosis was nearly doubled (phagocyte activity p < 0.0001, Candida uptake p < 0.003), T2 of respiratory burst was reduced by 65 % (p < 0.0001) and killing was accelerated by 27% (p < 0.046). However, the maximal activities of all kinetics were not altered. Incubation of phagocytes from healthy controls with B/T accelerated phagocytosis to a level comparable to that of untreated phagocytes from patients with XLA and also accelerated reactive oxygen species (ROS) production (reduction of HET by 28%, p < 0.012). In contrast to phagocytes from patients with XLA, phagocytes of patients with CVID showed a similar stimulation by B/T like healthy controls. Further experiments with the single substances showed that bromelain was the active compound. CONCLUSION: Our data suggest, that bromelain possesses immuno stimulatory properties. Phagocytes of XLA patients appear to be particularly susceptible to this stimulation.

PMID: 11410400 [PubMed - indexed for MEDLINE]

Inhibitory effect of enzyme therapy and combination therapy with cyclosporin A on collagen-induced arthritis.

Clin Exp Rheumatol. 2001 May-Jun;19(3):303-9.

Rovenska E, Svik K, Stancikova M, Rovensky J.

Research Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 01 Piest'any, Slovak Republic. rovensky@vurch.sk

OBJECTIVE: There is increasing interest in the use of combination therapy for rheumatoid arthritis and in the possibility of combining the conventional drug approach with newer antirheumatic therapy. The present study investigates the efficacy of long-term prophylactic enzyme therapy and combination therapy with cyclosporin A in rats with collagen-induced arthritis. METHODS: Rats with collagen-induced arthritis were administered the following drugs: cyclosporin A (5 mg/kg/day and 10 mg/kg/day orally); a mixture of enzymes containing pure substances (bromelain, trypsin, rutin) in the same ratio as in Phlogenzym (PHL, 150 mg/kg, twice daily intrarectally); and a combination of 5 mg/kg/day cyclosporin A plus 300 mg/kg/day PHL for a period of 50 days from the immunization. Levels of serum albumin, serum nitrite/nitrate concentrations, changes in hind paw swelling and bone erosions were measured in the rats as variables of inflammation and destructive arthritis-associated changes. RESULTS: Treatment with 10 mg/kg cyclosporin A, as well as combination therapy with half dosages of cyclosporin A (5 mg/kg) plus PHL significantly inhibited both inflammation and destructive arthritis-associated changes. Significant differences in favor of combination therapy with 5 mg/kg CsA + 300 mg/kg PHL as compared to 5 mg/kg CsA alone were seen in hind paw swelling. Also, reduction of the radiographic scores was more significant in the combination therapy group. Five mg cyclosporin A or PHL alone reduced the disease markers studied to a lesser extent, and in the case of enzyme therapy this occurred at a later stage of arthritis development. CONCLUSION: Our results show the inhibitory effect of enzyme therapy on collagen-induced arthritis in rats, as well as the efficacy of cyclosporin A given in low doses in combination with enzyme therapy, which may be useful in the treatment of rheumatoid arthritis.

PMID: 11407084 [PubMed - indexed for MEDLINE]

Enzyme and combination therapy with cyclosporin A in the rat developing adjuvant arthritis.

Int J Tissue React. 1999;21(4):105-11.

Rovenska E, Svik K, Stancikova M, Rovensky J.

Research Institute for Rheumatic Diseases, Piest'any, Slovak Republic. rovensky@vurch.sk

Recent knowledge of the pathophysiology of rheumatoid arthritis and the mechanism of drug effects have enabled the use of new drugs and drug combinations in rheumatoid arthritis therapy. This study investigates the efficacy of both enzyme therapy and combined therapy with cyclosporin in rats with adjuvant arthritis. Rats with adjuvant-induced arthritis were administered either cyclosporin A (2.5 or 5.0 mg/kg/day per os), a mixture of enzymes (Phlogenzym (PHL); 45 mg/kg twice daily intrarectally), or a combination of 2.5 mg cyclosporin A and 90 mg PHL for a period of 40 days from the adjuvant application. Levels of serum albumin, changes in hind paw swelling and bone erosions were measured in rats as variables of inflammation and arthritis-associated destructive changes. Treatment with 5 mg of cyclosporin A, as well as with the combination therapy with cyclosporin A plus PHL, significantly inhibited both the inflammation and destructive arthritis-associated changes. However, 2.5 mg of cyclosporin A and PHL alone inhibited these disease markers, although to a lesser extent and at a later stage of arthritis development. The results show the inhibitory effect of enzyme therapy on rat adjuvant arthritis, as well as the efficacy of a low dose of cyclosporin A given in combination with enzyme therapy, which may be useful in the treatment of rheumatoid arthritis.

PMID: 10761540 [PubMed - indexed for MEDLINE]

Natural treatment of perennial allergic rhinitis.

Thornhill SM, Kelly AM.

Altern Med Rev. 2000 Oct;5(5):448-54.

Northwestern Health Sciences University College of Chiropractic, Bloomington, MN 55431, USA.

Perennial allergic rhinitis is an IgE-mediated inflammatory disorder of the nasal mucosa characterized by paroxysms of sneezing, nasal congestion, pruritis, and rhinorrhea. The condition may be caused by certain environmental agents, food sensitivities, structural abnormalities, metabolic conditions, or synthetic drugs. Recent health impairment outcome studies on allergic rhinitis sufferers reveal a measurable decline in physical and mental health status and the inability to perform daily activities. Antihistamines, decongestants, anticholinergic agents, and corticosteroid drug therapy, alone or in combination, are typically used in the treatment of allergic rhinitis. Reported adverse side effects include sedation, impaired learning/memory, and cardiac arrhythmias. Therapeutic strategies should seek to decrease the morbidity already associated with this condition. Urtica dioica, bromelain, quercetin, N-acetylcysteine, and vitamin C are safe, natural therapies that may be used as primary therapy or in conjunction with conventional methods.

Publication Types:

• Review
• Review, Tutorial

PMID: 11056414 [PubMed - indexed for MEDLINE]

Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo.

In Vivo. 1999 Jan-Feb;13(1):7-12.

Metzig C, Grabowska E, Eckert K, Rehse K, Maurer HR.

Institute of Pharmacy, Free University of Berlin, Germany.

The thiol protease, bromelain, an extract from pineapple stem, was suggested to have antithrombotic and anticoagulant activities in vivo. We studied the effects of bromelain on cell size distribution of isolated human platelets in vitro by Coulter Counter measurements. Preincubation of platelets with bromelain (10 micrograms/mL) completely prevented the thrombin (0.2 U/mL) induced platelet aggregation. Papain was less active in preventing platelet aggregation. In vitro, bromelain (0.1 microgram/mL) reduced the adhesion of bound, thrombin stimulated, fluorescent labeled platelets to bovine aorta endothelial cells. In addition, preincubation of platelets with bromelain, prior to thrombin, activation, reduced the platelet adhesion to the endothelial cells to the low binding value of unstimulated platelets. On the basis of mass concentrations, the proteases papain and trypsin were as effective as bromelain. Using a laser thrombosis model, the in vivo effects of orally and intraveneously applied bromelain on thrombus formation in rat mesenteric vessels were studied. Bromelain, orally applied at 60 mg/kg body weight, inhibited the thrombus formation in a time dependent manner, the maximum being after 2 hours in 11% of arterioles and 6% of venoles. Intravenous application at 30 mg/kg was slightly more active in reducing thrombus formation in arterioles (13%) and venoles (5%), suggesting that orally applied bromelain is biologically active. These results may help to explain some of the clinical effects observed after bromelain treatment in patients with thrombosis and related diseases.

PMID: 10218125 [PubMed - indexed for MEDLINE]

Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients.

Oncol Rep. 1999 Nov-Dec;6(6):1191-9.

Eckert K, Grabowska E, Stange R, Schneider U, Eschmann K, Maurer HR.

Institut fur Pharmazie der Freien Universitat Berlin, Berlin, Germany.

The protease bromelain from pineapple was suggested for adjuvant therapy of malignant diseases. We studied immunological effects of an orally applied bromelain drug on 16 breast cancer patients in comparison with healthy donors. Bromelain was applied for 10 days with a daily dose of 3000 F.I.P. units and the immunocytotoxicity of blood monocytes and lymphocytes against the leukemic K562 and MDA-MB-231 mammary carcinoma target cells was determined in vitro. In addition, the expression of the cell surface markers CD44, CD16, CD11a and CD62L on lymphocytes and the secretion of IL-2 and IL-1beta from monocytes was measured. Patients leukocytes expressed lower bMAK-, MAK-, NK- and LAK-cell activities, compared with those from healthy donors. Orally applied bromelain increased the reduced bMAK- and MAK-cell activity of patients monocytes about 2-fold. When the patients were classified on the basis of bromelain effects on the monocytic cytotoxicity into bromelain responders and nonresponders, about 40% of the patients responded to bromelain with an increase of cytotoxicity from 7.8% to 54% (bMAK-cell activity) and from 16% to 47% (MAK-cell activity). Bromelain was less effective on the higher cytotoxicity of monocytes from healthy donors, but stimulated the secretion of IL-1beta from monocytes. In contrast, patient monocytes secreted no detectable IL-1beta, before, during and after bromelain treatment. Bromelain had no effects on the impaired patients NK- and LAK-cell activity, but reduced the LAK-cell activity of healthy donors. No IL-2 was found in the supernatants of untreated and treated lymphocytes from healthy donors. Bromelain reduced the expression of CD44, but weakly increased CD11a and CD62L expression on patient lymphocytes, whereas CD16 remained unchanged. In vitro bromelain application to lymphocytes had similar effects, with greater reduction rates of CD44 and CD16 expression. As to coagulation parameters in plasma of healthy donors, the activated partial thromboplastin time was increased from 38 to 46 sec, leaving prothrombin time and plasminogen unchanged. These data suggest, that orally applied bromelain stimulates the deficient monocytic cytotoxicity of mammary tumor patients, which may partially explain its proposed antitumor activity.

Publication Types:

• Clinical Trial

PMID: 10523679 [PubMed - indexed for MEDLINE]

[Reducing pain by oral enzyme therapy in rheumatic diseases]

Wien Med Wochenschr. 1999;149(21-22):577-80.

Klein G, Kullich W.

Sonderkrankenanstalt fur rheumatische Erkrankungen und Herz-Kreislaufkrankheiten der PVArb, Saalfelden.

Proteolytic enzymes have analgesic, effects, besides the wellknown antiinflammatory and edema-reducing properties. These analgesic effects are based on the inhibition of inflammation and in addition to that on direct influences on the nociceptors. All that explains the therapeutical effects of such enzymes in degenerative-rheumatic and soft tissue rheumatic diseases in which inflammatory or immunologic processes are not in the forefront. In recent years a significant reduction of pain in various rheumatic diseases, concerning these aspects, was shown in several clinical studies. The clinical trial in patients with periarthritis of shoulder showed statistical equivalence of pain reduction, whether they were treated with phlogenzym or diclofenac. Likewise in the trial of patients suffering from painful osteoarthritis of the knee, there was a statistical equivalence of the pain-scores, comparing diclofenac and enzymes. The study of painful vertebral syndromes again resulted in equivalence of the treatment with NSAIDs compared to therapy with enzymes.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial
• Review
• Review, Tutorial

PMID: 10666820 [PubMed - indexed for MEDLINE]

Prevention of murine EAE by oral hydrolytic enzyme treatment.

J Autoimmun. 1999 May;12(3):191-8.

Targoni OS, Tary-Lehmann M, Lehmann PV.

Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44106, USA.

Clinical trials that test the efficacy of Phlogenzym (consisting of the hydrolytic enzymes bromelain and trypsin and the anti-oxidant rutosid) as a treatment for T cell-mediated autoimmune diseases including multiple sclerosis (MS), type 1 diabetes and rheumatoid arthritis are presently ongoing. We tested the effects of Phlogenzym treatment in the murine model for MS, experimental allergic encephalomyelitis (EAE), a disease induced in SJL mice by immunization with proteolipid protein (PLP) peptide 139-151. Oral administration of Phlogenzym resulted in complete protection from EAE. In Phlogenzym-treated mice, the dose response curve of the PLP:139-151-specific T cell response was shifted to the right, that is, the primed T cells required higher peptide concentrations to become activated. Additionally, the T cell response to this peptide was shifted towards the T helper 2 cytokine profile. Both effects are consistent with an increased T cell activation threshold. In support of this interpretation, we found that the accessory molecules CD4, CD44, and B7-1 (all of which are involved in T cell co-stimulation) were cleaved by Phlogenzym, while CD3 and MHC class II molecules (which are involved in the recognition of antigens by T cells) and LFA-1 were unaffected. These data show the efficacy of oral Phlogenzym treatment in an animal model of T cell-mediated autoimmune disease and suggest that the protective effect might be the result of an increase in the activation threshold of the autoreactive T lymphocytes brought about by the cleavage of accessory molecules involved in the interaction of T cells and antigen presenting cells. Copyright 1999 Academic Press.

PMID: 10222028 [PubMed - indexed for MEDLINE]

Protein-G binding material from synovial fluid of rheumatoid arthritis patients induces unorthodox autoantibodies (IgG1 rheumatoid factor) in NZB, NZW and (NZB x NZW)F1 mice.

Eur J Immunol. 1994 Mar;24(3):684-91.

Abedi-Valugerdi M, Ridderstad A, Lettesjo H, Strom H, Moller E.

Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.

Our previous studies have demonstrated that injection of rheumatoid arthritis (RA) synovial fluid (SF) induces a marked increase mainly of IgG1 antibody-producing cells in autoimmune disease prone (NZB x NZW)F1 mice but not in CBA mice. In the present study, the in vivo effect of RA-SF on autoantibody production was tested in different strains of mice. Injection of RA-SF induced the production of unorthodox autoantibodies (IgG1 rheumatoid factor, RF) in young (NZB x NZW)F1 mice as well as in their parental strains NZB and NZW, but not in normal mice (CBA) or in mice with severe combined immunodeficiency, indicating that the response is not caused by a conventional immune response against RA-SF material. IgG1 RF production was rapidly induced and reached high levels already on day 7 and lasted for more than 90 days. The induction of IgG1 RF was not the result of polyclonal activation, since RA-SF did not stimulate the production of other antibodies, such as autoantibodies against double-stranded DNA, bromelain-treated mouse red blood cells, myosin, transferrin, cytochrome c, thyroglobulin or myoglobin or antibodies reactive with the hapten TNP. To elucidate the identity of the active substance in RA-SF, responsible for IgG1 RF production, bound and unbound material of RA-SF, eluted from a protein-G column was injected into (NZB x NZW)F1 mice. Only the protein-G binding material was active, indicating that the effect is mediated by autoantibodies or immune complexes in the synovial fluid. Further studies demonstrated that identical concentrations of protein obtained from a pool of normal human IgG or SF from seronegative RA and non-RA arthritides patients did not contain the same activity.

PMID: 8125137 [PubMed - indexed for MEDLINE]

Reactivity of mouse antibodies against bromelain-treated mouse erythrocytes with thrombin-treated mouse platelets.

Immunology. 1989 Mar;66(3):335-8.

Kawaguchi S.

Department of Microbiology and Immunology, Shimane Medical University, Japan.

The reactivity of mouse antibodies against bromelain-treated mouse erythrocytes (BrMRBC) with mouse platelets before and after thrombin treatment was assessed by flow cytometry. Anti-BrMRBC antibodies could bind to thrombin-treated platelets, although normal platelets were also weakly reactive with the antibodies. The binding of anti-BrMRBC antibodies to platelets was confirmed by complement-dependent lysis. It is suggested that thrombin-activated platelets may be a real target for anti-BrMRBC antibodies.

PMID: 2467876 [PubMed - indexed for MEDLINE]

On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects.

Planta Med. 1990 Jun;56(3):249-53.

Lotz-Winter H.

Bromelain, a standardized complex of proteases from the pineapple plant, is absorbed unchanged from the intestine of animals at a rate of 40%; in animal experiments it was found to have primarily anti-edema, antiinflammatory, and coagulation-inhibiting effects. These effects are due to an enhancement of the serum fibrinolytic activity and inhibition of the fibrinogen synthesis, as well as a direct degradation of fibrin and fibrinogen. Bromelain lowers kininogen and bradykinin serum and tissue levels and has an influence on prostaglandin synthesis, thus acting antiinflammatory. In in vitro and in animal studies, experimentally induced tumours could be inhibited by bromelain. Although many studies do not give extensive statistical data, the effects of bromelain in animal studies seem to be dose-dependent. Further investigations have to be carried out.

Publication Types:

• Review
• Review, Tutorial

PMID: 2203073 [PubMed - indexed for MEDLINE]

Activation of murine autoreactive b cells by interleukin 1-like factors released from synovial inflammatory cells of rheumatoid arthritis patients.

Autoimmunity. 1991;8(3):187-92.

Bazzichi L, Soletti AL, Ciompi ML, Garzelli C.

Institute of Medical Pathology, University of Pisa.

The effect of interleukin 1 (IL-1)-like factor(s), produced by cells isolated from the synovial fluids of rheumatoid arthritis (RA) patients, on an in vitro murine model of spontaneous autoimmunity, i.e., the development of plaque-forming cells (PFC) to bromelain-treated mouse red blood cells (Br-MRBC) in mouse peritoneal cell (PC) cultures, has been investigated. It has been found that IL-1-containing culture supernatants from cells isolated from joint fluids of RA patients, as well as recombinant IL-1, determine a marked increase in anti-Br-MRBC PFC development. Moreover, factor(s) of 10-20 KD molecular weight, with IL-1-like biological activity, capable of increasing the anti-Br-MRBC PFC development in mouse PC cultures, have been demonstrated in joint fluids from RA patients. The finding that synovial inflammatory cells produce factors that activate autoreactive B cells further supports the role of autoimmunity in the pathogenesis of rheumatoid arthritis, as self-perpetuing disorder.

PMID: 1932507 [PubMed - indexed for MEDLINE]

Isolation of a fibrinolysis enzyme activator from commercial bromelain.

Arch Int Pharmacodyn Ther. 1981 Nov;254(1):157-67.

Ako H, Cheung AH, Matsuura PK.

A fibrinolysis enzyme activator was isolated from commercial bromelain. This enzyme preparation is used medicinally. A by-product of bromelain production, the acetone still residue, was used as a starting material to develop an isolation scheme which began with reversed phase chromatography, was followed by ion exchange chromatography, and ended with ultrafiltration. It had polarity and ion exchange properties similar to those of a neutral amino acid. The active substance has no intrinsic fibrinolytic activity but appears to enhance the activity of one of the fibrinolytic enzymes. The presence of the fibrinolysis enzyme activator in commercial bromelain may explain some of the physiological and clinical effects observed following the oral administration of the enzyme preparation.

PMID: 7199897 [PubMed - indexed for MEDLINE]

Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients.

Med Hypotheses. 1980 Nov;6(11):1123-33.

Felton GE.

It has been established that a bromelain plasminogen activator will produce plasmin in rat experiments. In addition the plasmin cleaves Hageman factor in a way that leads to a strong release of kallikrein but a weak release of thrombin. A possible mechanism is suggested to explain how the body can maintain thrombin at a level too low to cause platelet aggregation but adequate to stimulate release of prostaglandins and enzymes for more than 24 hours from a single dose of the pineapple enzymes. Since bromelain therapy leads to formation of platelets with increased resistance to aggregation, it is obvious that the dominant endogenous prostaglandins being produced must be from the group that increases platelet cyclicAMP levels (prostacyclin, PGE1, etc.). The combination of fibrinolytic and antithrombic properties appear to be effective and two large scale tests on heart patients have shown a practically complete elimination of thrombosis.

PMID: 6256612 [PubMed - indexed for MEDLINE]

Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update.

J Ethnopharmacol. 1988 Feb-Mar;22(2):191-203.

Taussig SJ, Batkin S.

Department of Food Science and Human Nutrition, School of Tropical Agriculture, Unive